Micro Emulsion

Seminar on
MICRO-EMULSI N
Presented by : Nazeer Hasan

M.PHARMACY (Industrial Pharmacy)
Department of pharmaceutics.
Delhi Pharmaceutical Science and Research University (DPSRU).
● HISTORICAL BACKGROUND
● INTRODUCTION
● COMPOSITION
● ADVANTAGES
& DISADVANTAGES
● METHOD OF PREPARATION
● APPLICATIONS
● The Microemulsion concept was introduced
as early as 1940s by Hoar and Schulman who
generated a clear single-phase solution by
titrating a milky emulsion with hexanol.
● Schulman and co-worker (1959)

subsequently coined the term
microemulsion
● The microemulsion definition provided by

Danielson and Lindman in 1981 will be used
as the point of reference.
•Modern colloidal drug delivery
system
•Micro emulsions are clear,
transparent, thermodynamically
stable dispersions of oil and water,
stabilized by an interfacial film of
surfactant frequently in
combination with a co-surfactant.
•Diameter - 10-200 nm.
MICRO-EMULSI N
Microemulsions are mono-dispersed spherical droplets

(diameter < 100 nm) of water in oil or oil in water, with
presence of surfactants and co-surfactants, as seen in these
vials.
6
Cont…….
● In this type of system, the two liquids tend to separate
out in two layers.
● And to avoid this, a third substance called as an
emulsifier is added, act by:
● they tend to adsorb at interface, where they can fulfill
their dual affinity with hydrophilic groups located in
aqueous phase and hydrophobic groups in oil or air.
● they reduce the mismatch with solvent through a
specific kind of aggregation process known as
micellization
MAJOR GOALS
• To delivery of hydrophilic as well as lipophilic drug as

drug carriers because of its
• improved drug solubilization capacity,
• long shelf life,
• easy of preparation and
• improvement of bioavailability.
EMULSION Vs MICRO EMULSION:
Shape
Macro emulsion Micro emulsion

EMULSION Vs MICRO EMULSION:
Size
MACRO EMULSION Vs MICRO
EMULSION
FEATURES MACRO EMULSION MICRO EMULSION
DEFINITION Emulsions consist of roughly spherical They constantly evolve

droplets of one phase dispersed into the between various structures
other ranging from droplet like
swollen micelles to bi
continuous structure.
DROPLET 1 – 20 µm. 10 – 100 nm.

SIZE
APPEARANCE Most emulsions are opaque (white) Microemulsions are
because bulk of their droplets is greater transparent or translucent
than wavelength of light and most oils
have higher refractive indices than
water.
FEATURES MACRO EMULSION MICRO EMULSION
PHASES Two One
STABILITY Stable but coalesce finally More thermodynamically

stable than macroemulsions
PREPARATION Require intense agitation for Generally obtained by gentle

their formation. mixing of ingredients.
SURFACTANT 2-3 % Weight 6-8% by weight

CONCENTRATION
MACROEMULSION Vs MICRO
EMULSION
ADVANTAGES
● thermodynamically stable
● require minimum energy for formation.
● Ease of manufacturing and scale-up
● Improved drug solubilization and bioavailability.
● drug targeting and controlled release
● The formation of micro emulsion is reversible. They may
become unstable at low or high temperature but when the
temperature returns to the stability range, the micro emulsion
reforms.
● The use of micro emulsion as delivery systems can improve the
efficacy of a drug, allowing the total dose to be reduced and
thus minimizing side effects.
DISADVANTAGES
● Use of a large concentration of surfactant and co-
surfactant necessary for stabilizing the nanodroplets.
● Limited solubilizing capacity for high-melting
substances
● The surfactant must be nontoxic for using
pharmaceutical applications
● Micro emulsion stability is influenced by
environmental parameters such as temperature and
pH. These parameters change upon micro emulsion
delivery to patients.
Theories of Microemulsion formation
Solubilization • Packing ratio & CPP
theory • V/a*l
Thermodynamic • ∆G=−ve
theory • ∆G= γ ∆G
• Complex film formation at interface

Mixed Film • Due to co-surfactant.
theory
16
2
Oil
∆Gm = free energy change for microemulsion formation

∆G1 = free energy change due to increase in total surface area
∆G2 = free energy change due to interaction between droplets
∆G3 = free energy change due to adsorption of surfactant at the
oil/water interface from bulk oil or water
∆S = increase in entropy due to dispersion of oil as droplets
17
Why are microemulsions
thermodynamically stable?
ΔGm
ΔGm > 0 for C & D emulsion formation
D
C
R*
R
B
ΔGm*
A
ΔGm* < 0 for A & B in certain Rrange

↓
microemulsion formation in that R range
Microemulsions form spontaneously only when IFT is small. (order of 10-3

mN/m)
18
Formation of Microemulsion
● Micro emulsion is formed
when
● the interfacial tension at
the O/W interphase are
brought very low level.
● The interfacial tension
is kept highly flexible and fluid.
22
METHODS
Phase Titration Method
Spontaneous emulsification method depicted

with the help of phase diagrams
Phase Inversion Method

•occurs upon addition of excess of the dispersed phase or in
response to temperature
• These methods make use of changing the spontaneous
curvature of the surfactant.
•changing the temperature of the system, forcing a transition from
an o/w microemulsion at low temperatures to a w/o microemulsion
at higher temperatures
23
24
W/O micro-emulsions
• During preparatoin firstly Reverse micelles forms, to
minimise S. free energy
• They are dynamic i.e. micelles frequently collide via

random Brownian motion
Malik M.A. et al, Arabian Journal of Chemistry (2012) 5, 397–417 26

O/W micro-emulsions
• The charged head group of the microemulsion droplets is
the driving force for producing O/W micro-emulsion
• This also increases Temperature stability
• can be used as carriers for a wide number of organic
compounds

Bi-continous micro-emulsions
• Water and oil both are continuous phases
• Amount also comparable
• It is like sponge
• Encountered in microemulsions, in mesophases, and even
in relatively dilute surfactant solutions
• Indicated by the average mean curvature zero
• May also exist as hexagonal liquid crystal structure

Factors affecting micro emulsion
formation
● Packing ratio
● Property of surfactant
● Property of oil phase
● Temperature
● Chain length
● Type and nature of cosurfactant
APPLICATIONS
Pharmaceutical applications of microemulsions
● Increase bioavailability of
drugs poorly soluble in water
● Topical drug delivery systems
Preparation of nanoparticles from microemulsion
precursors
● Oral drug delivery
● Ocular drug delivery
● Pulmonary drug delivery
● Transdermal drug delivery
● Parenteral drug delivery
● For solubilization of drug
● In biotechnlogy
● others
Oral drug delivery
● Advantages of microemulsions:
● increased absorption
● improved clinical potency
● decreased drug toxicity
● Ritchel et.al(1990) studied the absorption of
cyclosporine (potent, cyclic endekapeptide).
● Poor bioavailability
● 2 w/o microemulsion-sorbitol ester polyoxyethylene
glycolmonoether. LMW alcohol, fatty ester and water.
Topical drug delivery
● Microemulsions may enhance transdermal drug delivery
primarily by the following effects:
● Micro emulsions can exhibit a high solubilization
capacity for both lipophilic and hydrophilic drugs, thus
more drug can be loaded into the microemulsion, which
increases the concentration gradient across the skin without
depletion.
● The reservoir effect of the internal phase maintains a
constant driving force of drug from the external phase to the
skin and prolongs absorption. Since the diffusion of the
drug into the skin only occurs from the external phase of
the micro emulsion, the internal phase continually supplies
drug to the external phase so that it remains saturated with
the drug.
Ocular and intranasal drug delivery
● For the treatment of eye diseases, drugs are essentially
delivered topically. O/W microemulsions have been
investigated for ocular administration, to dissolve
poorly soluble drugs, to increase absorption and to
attain prolong release profile.
● Hasse and keipett(1997) prepared microemulsion
containing pilocarpine were formulated using
lecithin,PG and PEG 200 as cosurfactant and IPM as
oil phase. The formulation had low viscosity with
refractive index leading to ophthalmic application
Parenteral Drug Delivery
● Parenteral administration (especially via the intravenous
route) of drugs with
● limited solubility is a major problem
● extremely low amount of drug actually delivered to a
targeted site.
● Microemulsion formulations have distinct advantages over
macroemulsion systems when delivered parenterally
because of
● the fine particle microemulsion is cleared more slowly than
the coarse particle emulsion and, therefore, have a longer
residence time in the body. Both O/W and W/O
microemulsion can be used for parenteral delivery.
Conclusion
● Microemulsions are optically isotropic and
thermodynamically stable liquid solutions of oil,
water and amphiphile.
● Microemulsions are readily distinguished from
normal emulsions by their transparency, low viscosity
and more fundamentally their thermodynamic
stability.
● Drug delivery through microemulsions is a promising
area for continued research with the aim of achieving
controlled release with enhanced bioavailability and
for drug targeting to various sites in the body.
39

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Seminar on

Presented by : Nazeer Hasan

● Schulman and co-worker (1959)

● The microemulsion definition provided by

Microemulsions are mono-dispersed spherical droplets

• To delivery of hydrophilic as well as lipophilic drug as

Macro emulsion Micro emulsion

DEFINITION Emulsions consist of roughly spherical They constantly evolve

DROPLET 1 – 20 µm. 10 – 100 nm.

PHASES Two One

STABILITY Stable but coalesce finally More thermodynamically

PREPARATION Require intense agitation for Generally obtained by gentle

SURFACTANT 2-3 % Weight 6-8% by weight

• Complex film formation at interface

∆Gm = free energy change for microemulsion formation

ΔGm* < 0 for A & B in certain Rrange

Microemulsions form spontaneously only when IFT is small. (order of 10-3

Spontaneous emulsification method depicted

Phase Inversion Method

• They are dynamic i.e. micelles frequently collide via

Malik M.A. et al, Arabian Journal of Chemistry (2012) 5, 397–417 26

Malik M.A. et al, Arabian Journal of Chemistry (2012) 5, 397–417 27

Malik M.A. et al, Arabian Journal of Chemistry (2012) 5, 397–417 28

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